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The phage-encoded protein PIT2 impacts Pseudomonas aeruginosa quorum sensing by direct interaction with LasR

Kaat Schroven1, Leena Putzeys1, Anne-Laure Swinnen1

  • 1Laboratory of Gene Technology, KU Leuven, 3000 Heverlee, Belgium.

Iscience
|September 22, 2023
PubMed

Insights

A novel phage protein, PIT2, effectively reduces the virulence of antibiotic-resistant Pseudomonas aeruginosa by inhibiting key secretion systems. This discovery offers a promising new strategy against multidrug-resistant bacterial infections.

Area of Science:

  • Microbiology
  • Bacteriology
  • Molecular Biology

Background:

  • Increasing antibiotic resistance in Pseudomonas aeruginosa necessitates novel therapeutic approaches.
  • Pseudomonas aeruginosa utilizes virulence factors, such as the type II secretion system (T2SS), to cause infection.
  • Targeting bacterial virulence pathways offers an alternative to traditional antibiotic treatments.

Purpose of the Study:

  • To investigate the potential of phage-derived proteins to attenuate Pseudomonas aeruginosa virulence.
  • To identify specific phage proteins that can inhibit the type II secretion system (T2SS) in P. aeruginosa.
  • To explore the impact of phage proteins on bacterial gene expression and virulence.

Main Methods:

  • Utilized RNA sequencing (RNAseq) for differential gene expression analysis.
  • Investigated the inhibitory effects of PIT2, a protein from Pseudomonas phage LMA2, on T2SS effectors (PrpL and LasA).
  • Assessed bacterial virulence in vitro using HeLa cells and in vivo using Galleria mellonella models.

Main Results:

  • The phage protein PIT2 successfully inhibited T2SS effectors PrpL and LasA.
  • PIT2 demonstrated significant attenuation of P. aeruginosa virulence in both cell culture and insect models.
  • RNAseq analysis revealed PIT2's impact on the LasR regulatory network, crucial for bacterial quorum sensing.

Conclusions:

  • Phage protein PIT2 is a potent inhibitor of P. aeruginosa T2SS and virulence.
  • PIT2 modulates bacterial quorum sensing pathways, offering a novel anti-virulence mechanism.
  • This research provides a foundation for developing phage-inspired anti-virulence strategies against multidrug-resistant P. aeruginosa.
Keywords:
MicrobiologyVirology

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